Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of pancreatic neoplasms that originate from the endocrine cells of the pancreas, whose prevalence and incidence are constantly increasing worldwide. Based on current knowledge of their natural history, pNETs can be divided into functioning pNET and nonfunctioning pNET tumors, characterized by hormone hypersecretion, which results distinct clinical presentations. Treatment options include observation, medical or surgical therapy, and the choice depends on various factors such as staging and grading of the pancreatic lesion and the presence of a specific hormonal syndrome. Surgical resection has long been considered the gold standard for treatment, with related risks of morbidity and mortality. Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) plays a crucial role as minimally invasive procedure for loco-regional treatment of pNETs in selected patients, showing promising results in terms of clinical outcome. EUS-RFA causes a coagulative necrosis with minimal damage to surrounding tissue, allowing for local ablation. This review summarizes the most recent evidences on the use of EUS-RFA as local ablation therapy describing the main endoscopic steps and providing a critical overview of patient selection criteria, side effects, and long-term outcomes.

The role of pulmonary metastasectomy has been increasingly questioned in the surgical community after the PulMiCC trial challenged its benefit in colorectal cancer. However, the view on pulmonary metastasectomy among people in non-surgical disciplines remains unclear. This study explored interdisciplinary attitudes toward pulmonary metastasectomy and identified the clinical expectations shaping its future role. An anonymous online survey of active board-certified physicians in oncology, urology, gynecology and dermatology was conducted (December 2024-June 2025). Twenty items covered attitudes to local ablative therapy, referral criteria, preferred modalities and future relevance. Group comparisons used Pearson's χ2; ordinal ratings were compared by one-way ANOVA; associations were explored with Spearman's ρ. Of 2884 contacted physicians, 165 participated (≈5.7%), and 106 completed the questionnaire. All 106 (100%) endorsed local ablative therapy as meaningful; 92/106 (86.8%) favored routine integration into multimodal care. Surgical metastasectomy was selected by 49/106 (46.2%), SBRT was selected by 27/106 (25.5%) and image-guided ablation was selected by 7/106 (6.6%); preference for surgery differed by specialty (χ2(4) = 15.31, p = 0.004), while institutional availability (in-house thoracic surgery or radiation oncology) showed no association with selecting surgery or SBRT. Key referral determinants were number of lesions (105/106; 99.1%), anatomical location (86/106; 81.1%; p < 0.02 across specialties), and lesion size (81/106; 76.4%; p < 0.05); other factors showed no consistent inter-specialty differences. The perceived usefulness of metastasectomy was high (mode 8/10) and showed a weak, non-significant correlation with referral experience (ρ = 0.172, p = 0.077). Looking ahead, 46/106 (43.4%) anticipated a declining role of local ablative therapy with novel systemic therapies; interest in biomarker analysis from metastatic tissue compared to primary tumor tissue was very high 97/106 (91.5%). Local ablative therapy, particularly pulmonary metastasectomy, continues to be viewed as an integral and trusted element of metastatic disease management across specialties. Despite limited prospective evidence, clinicians maintain strong confidence in its clinical value and foresee its evolution toward biologically and patient-tailored indications. However, the interpretation of these findings is limited by a low response rate and potential selection bias toward European, academically affiliated respondents. To our knowledge, this is the first study to systematically capture perceptions of pulmonary metastasectomy among non-surgical oncology-related specialists.

Malignant hilar biliary obstruction (MHO), most commonly caused by cholangiocarcinoma, is an aggressive condition with a poor prognosis. Because most patients with MHO are unsuitable for primary surgical resection at presentation because of advanced age or comorbidities, palliative biliary drainage is essential to relieve obstructive jaundice and improve the quality of life. Endoscopic drainage has become the preferred palliative approach, with the choice between plastic and metal stents depending on subsequent therapeutic plans, such as systemic chemotherapy or local ablative therapies. Among biliary stents, self-expandable metal stents (SEMSs) are widely used, typically in their uncovered form. However, unlike plastic stents, uncovered SEMSs cannot be removed once deployed, and endoscopic revision is technically challenging. To improve stent patency and facilitate removability, covered SEMSs (CSEMSs) were developed, and are now commonly used in distal malignant biliary obstruction. Nevertheless, in advanced MHO, the primary use of CSEMSs remains controversial. This review summarizes recent endoscopic strategies for advanced MHO, the evolution of CSEMSs, their clinical outcomes, current limitations, and future directions.

To ablate or not to ablate? Outcomes of local ablative treatments (LAT) for oncogene addicted (OA) oligo-metastatic (OM) non-small cell lung cancer (NSCLC): A systematic review.

Pattern of failure, impact of local therapy, and characteristics of long-term responders with advanced EGFR mutation positive non-small cell lung cancer treated with first-line osimertinib.

Oligometastatic soft tissue sarcoma (STS) may offer the possibility of cure compared with polymetastatic disease, with progression patterns and treatment responses varying across histologic subtypes. This study investigated the clinical characteristics, oncologic outcomes, and histologic subtype-specific features of oligometastatic STS. We reviewed records of 1,243 patients with extremity/trunk STS who underwent curative surgery between 2000 and 2023. Oligometastatic recurrence occurred in 170 (13.6%), 149 of whom received local ablative therapy (LAT). Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed, along with prognostic factors and subtype-specific characteristics. The median follow-up was 52.5 months. Surgery alone was the most common LAT (71.2%), followed by surgery with radiotherapy, radiotherapy alone and radiofrequency ablation. The median DSS was 50.0 months (95% confidence interval [CI], 31.5-68.5), with a 5-year DSS rate of 45.2%. The median PFS was 12.0 months (95% CI, 7.6-16.4), with a 5-year PFS of 28.1%. On multivariate analysis, LAT was independently associated with longer DSS (hazard ratio [HR], 9.629; p<0.001). Smaller oligometastatic lesion size and adequate local control of the primary tumor were also independently associated with longer DSS. Metastasis-free interval > 6 months independently predicted longer PFS. Histologic subtypes demonstrated distinct clinical behaviors; for example, myxofibrosarcoma had a lower metastatic rate but poorer DSS, whereas synovial sarcoma showed relatively favorable long-term survival. Oligometastatic STS represents an intermediate disease state in which LAT can provide meaningful survival benefit. Subtype-specific differences in metastatic behavior and survival outcomes would support individualized, multimodal, and potentially curative treatment strategies.

Simple SummaryThe use of neoadjuvant therapies in patients with hepatocellular carcinoma prior to liver transplantation has gained increasing relevance in recent years, yet evidence regarding their impact on post-transplant outcomes remains limited. This study aimed to assess the effect of neoadjuvant therapies on overall survival following liver transplantation in patients with hepatocellular carcinoma and to compare outcomes across treatment modalities with respect to tumor burden. A total of 107 patients were analyzed, including 90 who underwent neoadjuvant treatment. Therapeutic strategies comprised SIRT, TACE, liver resection, and combined SIRT/TACE. Neoadjuvant therapy was associated with a significant survival benefit after liver transplantation. TACE demonstrated the greatest efficacy in patients meeting established transplant criteria, typically characterized by lower tumor burden, whereas SIRT conferred superior benefit in patients with higher tumor burden or those beyond conventional listing criteria.Background: The use of neoadjuvant therapies in patients with hepatocellular carcinoma prior to liver transplantation has gained increasing popularity in recent years. To date, there are only limited data investigating the impact of neoadjuvant therapy on post-transplant survival. Methods: In this retrospective study, we evaluated patients with hepatocellular carcinoma who underwent deceased donor or living donor liver transplantation at Jena University Hospital between 2019 and 2023. Comprehensive clinical and pathological variables were systematically analyzed, including correlations between neoadjuvant therapy use, tumor burden and overall survival. Survival outcomes were estimated using the Kaplan–Meier method. Results: A total of 107 patients were included in the analysis, of whom 90 received neoadjuvant therapy prior to transplantation. Treatment modalities comprised SIRT, TACE, liver resection and combined SIRT and TACE. The 1-, 3-, and 5-year OS rates following transplantation were 93.5%, 82.2%, and 79.4%, respectively. Recurrence-free survival at 1, 3, and 5 years was 91.6%, 85.0%, and 83.2%, respectively. Among the various neoadjuvant strategies, SIRT and TACE yielded the highest OS rates. Patients listed outside the transplantation criteria (Milan, UCSF, up-to-seven) at the time of initial diagnosis who underwent SIRT had significantly better OS than those outside the criteria who underwent TACE. In contrast, among patients within the Milan, UCSF and up-to-seven criteria, TACE was associated with superior OS compared with SIRT. Conclusion: The use of neoadjuvant therapies confers a significant survival benefit following liver transplantation in patients with HCC. TACE appears to be most suitable for patients listed within established transplantation criteria, who consequently have a lower tumor burden. In contrast, SIRT is more beneficial for patients with a higher tumor burden and those beyond standard transplantation criteria. A limitation of our study, however, is that the included SIRT cohort comprised only 24 patients, and TACE was preferentially performed in patients with a lower tumor burden, which means that a selection bias cannot be fully excluded. Overall, further studies are required to define the optimal bridging strategies.

IntroductionThe Weighted Alpha-Fetoprotein Tumor Burden Score (WATS) shows promise for hepatocellular carcinoma (HCC) prognosis, but its usefulness in local ablation patients is uncertain, and no validated nomograms exist for overall survival (OS) prediction.MethodsThis retrospective study enrolled 862 HCC patients who underwent local ablation therapy at Beijing You’an Hospital between January 1, 2015 and December 31, 2022. Participants were randomly allocated into a training cohort (n=603) and validation cohort (n=259) in a 7:3 ratio. Based on the median value of the WATS score, patients were stratified into low-risk (n=431) and high-risk (n=431) groups. The Kaplan-Meier (KM) curve was used to compare the prognosis between the two groups. Potential prognostic factors were screened via least absolute shrinkage and selection operator (Lasso) regression, followed by construction of a WATS-incorporated nomogram prediction model using Cox proportional hazards regression. The SHapley Additive exPlanations (SHAP) method was employed to interpret variable contributions within the model. Model performance was evaluated via Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Patients were stratified into low- and high-risk groups according to the nomogram scores, and KM curves were used to compare OS differences between the two groups.ResultsThe study identified the WATS, age, history of drinking, and prealbumin as independent prognostic factors for OS, and successfully established a nomogram model for OS prediction. The ROC curves, calibration curves, and DCA all confirmed that the model possesses good discriminative ability, calibration accuracy, and clinical utility. KM curves demonstrated that the nomogram could effectively stratify patients into different risk categories with satisfactory predictive performance.ConclusionThis study developed and validated a novel prognostic nomogram incorporating the WATS to assess OS in HCC patients receiving local ablation therapy. The nomogram demonstrated robust discriminative ability, enabling accurate prediction of 3-, 5-, and 8-year OS rates, thereby providing clinicians with a reliable tool for individualized risk assessment and treatment decision-making.

A multi-institutional dummy run on segmentation variability and plan quality of stereotactic body radiotherapy for oligometastatic disease

Nanostrategies synergize with locoregional interventional therapies for boosting antitumor immunity.

2061eP Effectiveness of adding local ablative therapy to first-line tyrosine kinase inhibitor therapy in epidermal growth factor receptor-mutated oligometastatic non-small cell lung cancer: A systematic review and meta-analysis

BackgroundLung cancer remains the leading cause of cancer-related mortality globally. In recent years, the advent of image-guided percutaneous ablation techniques has led to a gradual increase in the application of local ablation therapy (LAT) for both primary and secondary lung malignancies. Despite this progress, a systematic summary of the research trends and current clinical applications in this field is still lacking. Bibliometric analysis, a powerful statistical and visualization tool, can provide valuable insights into the evolving landscape of this therapeutic modality. This study aimed to examine the utilization of LAT for both primary and metastatic lung cancers, while exploring current research focuses and potential future directions in this field.MethodsBy leveraging the Web of Science (WOS) core collection database, this study employed VOSviewer and bibliometrix tools to analyze current research trends and future development directions of LAT for both primary and metastatic lung cancers.ResultsThe study findings revealed a steady increase in annual publication volume between 2008 and 2023. Research output was predominantly contributed by China, the United States, and Japan. Among institutions, Memorial Sloan Kettering Cancer Center led in publication count, with Shandong University and Okayama University following closely. The Journal of Vascular and Interventional Radiology emerged as the most prominent journal in this research domain. Through keyword analysis, five major research clusters were identified: (I) therapeutic technologies for lung cancer; (II) ablation methodologies for non-small cell lung cancer (NSCLC); (III) interventional approaches and strategies for lung cancer; (IV) ablation techniques for metastatic lung tumors; and (V) innovative technologies in lung cancer treatment.ConclusionsLocal ablation combined with other treatments are expected to improve therapeutic effects and become future trend in the treatment of lung malignancies.

BACKGROUNDSeizure is a common and potentially disabling complication of brain metastasis (BrM). Local ablative therapies for BrM, including surgical resection with adjuvant stereotactic radiosurgery and stereotactic radiosurgery alone, have undefined seizure outcomes. We sought to define and compare these outcomes in patients with epileptogenic brain metastasis treated with either modality. METHODSPatients who received definitive stereotactic radiosurgery (SRS) or neurosurgical resection (R) plus adjuvant SRS for BrM at an NCI-designated Comprehensive Cancer Center between 2015 and 2023 were retrospectively reviewed. Patients with seizure and semiology attributable to an active, previously untreated metastasis were included. Clinical characteristics were extracted from the medical record. Actuarial estimates and Cox proportional hazards models compared seizure outcomes between modalities. RESULTSR+SRS (n=75) and SRS (n=103) groups were similar in baseline characteristics, but R+SRS patients had larger tumor diameter (mean [SD]: 2.80 [0.833] vs. 1.87 [0.668] cm; p<0.001). Radiation course also differed by treatment (% R+SRS vs. SRS patients [dosage in Gy, fractions]: 57.3% vs. 17.5% [30,5], 30.7% vs. 48.5% [27,3], 1.3% vs. 21.4% [21,1], 10.7% vs. 12.6% [other]; p<0.001). R+SRS patients were more likely to be seizure-free at 6-months post-treatment compared to SRS patients (estimated seizure-free probability [95%CI]: 0.860 [0.784,0.945] vs. 0.667 [0.577,0.770]; p=0.002) despite similar rates of active anticonvulsant use (85.7% vs. 82.6%; p=0.644). Under the univariate Cox model, R+SRS treatment demonstrated a 65.5% reduction in 6-month seizure recurrence hazard relative to SRS treatment (HR=0.345; 95%CI [0.169,0.703]; p=0.003). After adjustment for significant covariates including race, tumor diameter, and radiation dose and fractionation, this trend persisted (HR=0.413; 95%CI [0.179,0.955]; p=0.039). CONCLUSIONPatients with BrM-related seizures treated with resection and adjuvant stereotactic radiosurgery demonstrated greater 6-month seizure freedom and reduced post-treatment seizure hazard compared to those treated with radiosurgery alone. This discrepancy should be considered in local treatment planning for BrM.

Local Ablative Therapy Followed by Osimertinib Rechallenge in Oligoprogressive, EGFR-Mutated NSCLC: A Phase 2 Study

Oligometastatic non-small-cell lung cancer (OMD-NSCLC) has emerged as a biologically and clinically distinct subtype of advanced disease, characterized by limited metastatic burden and a more indolent course. In this narrative review, we examine the current definition of OMD-NSCLC, diagnostic tests, possible biomarkers, and current therapeutic strategies. Biological insights highlight the role of microRNAs in differentiating true oligometastatic state from polymetastatic disease. The main local ablative therapies (LAT) include surgery and radiotherapy. The integration of LAT with systemic therapies has been explored in clinical trials, yielding promising but occasionally inconsistent results. As the therapeutic landscape of OMD-NSCLC patients continues to evolve, refining definitions, identifying predictive biomarkers, and individualizing care are essential steps toward achieving the potential of radical-intent therapy.

During the systemic treatment of patients with non-small cell lung cancer (NSCLC), oligoprogression (OP), a condition in which most lesions remain controlled while a few progress or develop, has recently attracted attention. Traditionally, systemic therapy is continued after disease progression; however, advancements in local ablation therapy (LAT), such as radiotherapy and surgery, have demonstrated clinical efficacy in patients with OP. The characteristics of patients who may benefit from LAT or their genetic background remain unclear. This study evaluated the frequency, clinicopathological characteristics, and efficacy of LAT in the treatment of OP. A retrospective review was conducted of 510 patients with NSCLC who experienced disease progression after systemic therapy. Overall, 106/510 (23.6%) patients exhibited OP; among these, six patients who received only the best supportive care after OP were excluded. Systemic therapy alone was administered to 79 patients (79.0%), while 21 (21.0%) received LAT. Median local progression-free survival was numerically longer in the LAT group than in the systemic therapy-only group (8.3 and 6.7 months, respectively; p = 0.38). In addition, overall survival was also numerically longer in the LAT group than in the systemic therapy-only group (78.1 and 55.1 months, respectively; p = 0.57). Ribonucleic acid sequencing revealed an increase in extracellular matrix-related gene expression after OP, providing potential molecular insights. Although this study found no significant prognostic benefit of LAT in patients with OP, future research integrating clinical and molecular data may identify patients most likely to benefit from LAT.

Hepatocellular Carcinoma (HCC) ranks among the most prevalent human cancers and stands as the third most common cause of death related to cancer globally. Current therapies for HCC include surgical resection, local ablation, chemoembolization, liver transplantation, and molecular-targeted therapy. Only a small number of patients are detected in the early stage, and most patients are diagnosed at the time of the middle and late stages, thus losing the opportunity for surgical treatment, which is an essential reason for the high mortality of HCC patients. Initiating cytotoxicity in cancer cells stands as a fundamental approach for tumor treatment, with the majority of research centering on apoptosis. Since anti-apoptotic methods often fulfill cancer cells' ability to resist anticancer drugs, research on new induction forms of regulative cell death, such as ferroptosis, is of great clinical value. In this study, we employed a combination of in silico molecular docking and invitro cell validation experiments to identify three ferroptosis suppressor genes, AR, HIF1A, and CA9, as promising components of a survival prognosis model during the metformin-induced ferroptosis process in liver cancer. Further, we discovered that AR could achieve efficient molecular docking with Metformin among these genes. Additionally, cell experiments revealed that Metformin could downregulate the protein expression level of AR. This research has developed a prognostic model for ferroptosis suppressor genes through the analysis of the ferroptosis process induced by metformin in liver cancer. It also screened and validated AR as a potential molecular docking target for metformin.

Abstract Background: The term oligoprogression (OP) refers to a clinical scenario in which patients with diffuse metastatic disease on systemic therapy have a limited number of metastases that have progressed or are new whereas the majority of metastases are stable or improved. OP disease is increasingly being encountered in clinical practice due to improvements in systemic therapy. Treating OP disease with local ablative therapies may therefore prolong the time to more diffuse progression necessitating a change in systemic therapy and may therefore lead to improved overall survival in these patients. Only one study has evaluated the role of SBRT in patients with OP MBC. This trial accrued 47 patients with OP MBC, with 2/3 having triple negative disease. There was no difference in PFS between patients that received SBRT versus those that did not (4.2 months vs. 4.4 months, p=0.2). Whether ablative therapies are beneficial in subtypes of breast cancer that have many effective systemic therapies available, such as ER+ breast cancer, remains an open question and an unmet clinical need. Trial Design: Phase II study for patients with OP ER+ MBC (1-4 new and/or progressing metastatic lesions). Eligible patients will receive stereotactic body radiation therapy (SBRT) to the OP lesions. SBRT will be delivered to each lesion in 3-5 fractions. Each patient’s systemic therapy regimen will be held during study therapy and will resume upon completion of study therapy. Patients will then be restaged at 12 weeks post-SBSRT. Patients that have at least stable disease at that time point will continue on their systemic therapy and then be re-staged 12 weeks later (24 weeks after SBRT). This study will also study the role of ER-targeted positron emission tomography (PET) imaging with 16α-18F-Fluoro-17β-Fluroestradiol (FES) in the OP ER+ patient population with FES PET scans obtained at baseline, and at each of the 2 follow-up imaging timepoints. A key secondary hypothesis is that the use of FES PET in addition to standard imaging at baseline and in follow-up will help confirm patients have OP disease and will help assess for new lesions on subsequent restaging. Eligibility: Key inclusion criteria: age≥18 yo; histologically confirmed ER+/HER2- metastatic breast cancer; the presence of metastatic breast cancer at the time of study entry with progression in 1-4 lesions (including new lesions); SBRT must be feasible for all progressing lesions. Key Exclusion Criteria: &amp;gt;2 lines of systemic therapy for metastatic disease; intracranial disease progression Primary Objective: To determine whether using SBRT to treat OP lesions allows ER+ breast cancer patients to continue on their current systemic therapy for at least 24 weeks post SBRT. Select Secondary Objectives: To assess whether FES-PET increases the number of lesions found prior to SBRT; To determine the impact of SBRT on patient quality of life; time to next line systemic therapy; PFS Statistical Methods Simon 2 stage optimal design with α=0.05 and 1-β=0.80. The null hypothesis is that the proportion of patients that remain on their original systemic therapy ≥24 weeks (2 restaging scans) post-treatment is 20%. The alternative hypothesis is that the proportion of patients that remain on their original systemic therapy after 2 restaging scans is 50%. In stage 1, 8 patients that proceed to SBRT will be enrolled. The study will be terminated if only 0 or 1 subjects remain on original systemic therapy after 2 restaging scans. However, if ≥2 patients remain on original systemic therapy after 2 restaging, then an additional 10 patients would be enrolled for a total of 18 patients. The null hypothesis will be rejected if ≥6 patients remain on their original systemic therapy after 2 restaging scans.Contact Information: Jose G. Bazan (jbazan@coh.org) Funding Source: City of Hope Comprehensive Cancer Center and GE Healthcare Citation Format: Jose Bazan, Joanne Mortimer, Yun Rose Li, Rebecca Nelson, Sharon Yim. Stereotactic Body Radiation Therapy and FES PET/CT Imaging for the Treatment of Oligoprogressive Estrogen Receptor Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-30.

e15524 Background: MSS tumors account for 95% of metastatic colorectal cancer and are characterized by a low response rate to immunotherapy. Emerging evidence showed that radiotherapy combined with chemotherapy and PD-1 inhibitors led to promising tumor responses in patients (pts) with locally advanced rectal cancer (LARC). MIRACLE-1 aims to investigate the safety and efficacy of such approach as upfront treatment of MSS LARC with resectable metastases. Methods: MIRALCE-1 was a prospective, single arm, phase 2 study. The main inclusion criteria include MSS LARC with a distance of ≤10 cm from the anus by MRI evaluation and a limited number of metastases in the liver and/or lungs that were eligible for curable resection. Eligible patients were treated with upfront radiotherapy including hypofractionated radiotherapy (HFRT) for primary lesions and HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions. Afterwards, six cycles of systemic therapy consisted of CAPOX and Tislelizumab were administered. Then, reassessment was performed within 4 weeks afterwards by radiological and serological evaluations. Surgical resection, local ablative therapies or active surveillance was applied based on tumor response. For patients attained no-evidence of disease (NED), Tislelizumab was maintained until one year after surgery. Otherwise, the subsequent treatment was determined by the investigators. The primary endpoint is the 1-year NED rate. The secondary endpoints include objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicities. Results: From March 2023 to November 2024, 38 pts were enrolled and 20 were evaluable. At baseline, 60.0% of pts were male, median age was 57 years (range 34-71), 55.0% had liver metastases (mets), 15.0% had lung mets, and 30.0% had both liver and lung mets. 80.0% primary tumors had RAS/BRAF mutations. Upon reassessment, 18 (90.0%) pts had partial response (PR) and 2 (10.0%) had stable disease (SD). No patients showed progressive disease (PD). The ORR was 90.0%. 65% (13/20) pts attained NED. Median PFS and OS have not yet reached. No grade 5 adverse events occurred. The most common treatment-related adverse events (TRAEs) in all grades were fatigue (85.0%), thrombocytopenia (65.0%), leukopenia (50.0%) and anemia (40.0%). The most frequent grade 3/4 TRAEs were thrombocytopenia (30.0%) and neutropenia (20.0%). Conclusions: Combination treatment of upfront radiotherapy, immunochemotherapy demonstrated a promising efficacy and a manageable safety profile in MSS LARC with resectable metastases. Translational study to identify predictive biomarkers is ongoing. Clinical trial information: NCT05359393 .

e20535 Background: For patients with de-novo oligometastatic non-small cell lung cancer (NSCLC), combining local ablative therapy (LAT) with systemic treatment may offer extended survival. However, the imaging-based definition of oligometastatic disease (OMD) includes both patients with limited metastatic potential and favorable response to systemic treatment, as well as those harboring occult micrometastases prone to rapid progression. Prognostic biomarkers are thus critical to guide local and systemic treatment approaches. Although circulating tumor DNA (ctDNA) represents a promising biomarker, early studies have limited follow-up. Therefore, we investigated the prognostic value of ctDNA for long-term survival beyond 5 years in this patient population. Methods: This prospective study included patients with plasma liquid biopsy performed at the time of metastatic NSCLC diagnosis, treated between 2014 and 2019. ctDNA was analyzed using the validated ResBio ctDx-Lung assay, which targets up to 23 genes and enables the sensitive detection of variant allele frequencies (VAF) &gt;0.1%. Patients ≤5 disease sites on imaging were classified as having OMD, other as polymetastatic disease (PMD). Results: Among 623 patients, 103 (16.5%) had OMD, and 520 (83.5%) had PMD. Overall, ctDNA was detected in 405 patients (65.0%). Patients with OMD were less likely to have ctDNA detected (39.8% vs. 70.0%; p&lt;0.001), and had a significantly lower median VAF (1.1% vs. 2.9%; p=0.012) if ctDNA was detected. The median age was 67 years (range: 27–93). Driver mutations were detected in tumor tissue of 412 (66.1%) patients, most commonly in EGFR (n=171, 27.4%) and KRAS (n=127, 20.4%). Immune checkpoint inhibitors were given in 301 (48.3%), and targeted therapy in 282 (45.3%). Among patients with OMD, 48 (46.6%) received LAT of metastases and primary tumor at diagnosis. After a median follow-up of 68.6 months, 478 deaths were recorded. Median overall survival (OS) was significantly longer in patients with OMD compared to those with PMD (30.8 vs. 16.4 months, p&lt;0.0001). The 5-year OS rate was 31.1% (95% CI: 23.0–42.0) for OMD and 15.0% (95% CI: 12.0–18.8) for patients with PMD. On univariate Cox regression, OMD (HR: 0.57, p&lt;0.001) and driver mutations in tissue (HR: 0.81, p=0.034) correlated with improved OS, whereas ctDNA detection (HR: 1.94, p&lt;0.001) and higher VAF (HR: 1.01, p=0.017) were associated with worse OS. Multivariate Cox regression confirmed the significant association of ctDNA detection (HR: 1.88, p&lt;0.001), OMD (HR: 0.69, p=0.005) and driver mutations (0.77, p=0.008) with OS. Conclusions: Long-term survival beyond 5 years was observed in more than 30% of patients with NSCLC and OMD, with ctDNA detection and maximum VAF demonstrating prognostic value. Integration of ctDNA with radiographic stratification could enhance patient selection for combined local and systemic treatment approaches.